Saliva is an important diagnostic fluid that has the potential to be used for detection of essential biomarkers for both oral and systemic diseases. Unfortunately, the current lack of reliable detection methods for measurement of important analytes within this complex biomatrix has hindered progress in salivary diagnostics. To help remove this barrier, recent promising activities have been initiated in microfluidic-based Lab-on-a-Chip (LOC) systems. While several miniaturized platforms are being developed now, few of these systems have evolved to the point where important protein biomarkers can be measured over the physiological range using real saliva samples. Towards this essential goal, the team of investigators from UT and UK have developed and documented carefully an integrated biochip assay system that is suitable for measurement of panels of important inflammatory markers (e.g. CRP, IL-1beta, MMP-8, TNF-alpha, IL-6) in saliva. This newly fashioned ultra-sensitive method has been used to extend saliva-based diagnostics to the low levels of CRP found in saliva, therefore allowing for the first comparison of CRP levels between healthy, periodontitis, and edentulous patients. The miniaturized system correlates nicely with established macroscopic gold standard methods. Thus, it now important to take the next steps to combine these functional components and associated methodologies so as to create a flexible platform system that may be used to promote and expand the field of salivary diagnostics. This U01 renewal program targets the development of portable devices that can be used to complete salivary diagnostic tests. The program will evolve with important biochip, analyzer and immunoassay development milestones to be completed in the first two years of the program. In year 1, integrated biochips and analyzers will be developed and tested. These alpha prototypes will be used to define specifications for more final systems. In year 2, fully developed biochips and analyzer suitable to serve, as beta prototypes will be fashioned. These highly functional portable systems will be used in years 3-5 to complete pre-clinical testing and validation. Salivary biomarker fingerprints that our team has already defined will be used to 1) discriminate stages of periodontitis and 2) identify risk for future cardiac events in coronary artery disease patients. Final data acquisition and FDA approval will be completed by year 5.